The major aims of this collaborative depression study are: (1) to test critical hypotheses implicating biochemical and neuroendocrinological mechanisms in the etiology and maintenance of depressive states: (2) to confirm or disconfirm hypotheses concerning current psychobiologic theories of depression; (3) to explore and to to extend behavioral - biologic interaction in clinical depression and (4) to define empirically clinical and biologic subgroups of affective disorders. The study aims particularly to explore the possibility that the genesis of the affective disorders resides in interaction between the activity of systems and not in a deficit in a single system, for example, relationships between the serotonergic and noradrenergic systems and how they may respond to neuroendocrine or electrolyte changes. Batteries of biochemical, clinical and behavioral measures are being taken simultaneously from patients and from selected comparison groups. Cornell's specific assigment in this project, in addition to patient data collection is to analyze some of the neuroendocrinological and enzyme data generated by all five participating centers. The goals for this year (1975-76) include drafting a final protocol, training of staff, acquisition of necessary equipment, determination of laboratory procedures, and the beginning of data collection with preliminary analysis. Principal and assistant principal investigators have met with those from other centers on several occasions in New Haven, Washington, D. C. and twice here in New York. The principal investigators have held biweekly telephone conferences to identify, discuss and make decisions about problems as they arise. A final working protocol was put into effect by the middle of March 1976. To date, a total of 4 patients have completed the study protocol at Cornell (2 patients in experimental group 1 - unipolar depression, primary type; 1 patient in experimental group 2 - bipolar depression, primary type; and one patient in control group 2 - chronic schizophrenia). The New York meeting in January 1976 provided collaborative training for the investigators in the use of Research Diagnostic Criteria and the Schedule for Affective Disorders and Schizophrenia.